Epithelial cell cancers, for example, prostate cancer, breast cancer, colon cancer, lung cancer, pancreatic cancer, ovarian cancer, cancer of the spleen, testicular cancer, cancer of the thymus, etc., are diseases characterized by abnormal, accelerated growth of epithelial cells. This accelerated growth initially causes a tumor to form. Eventually, metastasis to different organ sites can also occur. Although progress has been made in the diagnosis and treatment of various cancers, these diseases still result in significant mortality.
The treatment of cancer is greatly enhanced by early detection. However, there are difficulties in detecting the disease in its early stages. For example, epithelial tissue-containing organs such as the prostate, ovary, and others, are not easily palpated. The detection of abnormal tumor growth in such organs is difficult without frequent screening and appropriate markers. A substantial drawback of available cancer diagnostic assays is a high rate of false positive and negative results, making the available tests less reliable than desired. For this reason, there is a great need to identify new diagnostic as well as new therapeutic agents to improve diagnosis and treatment of cancer, for example, prostate cancer, breast cancer, colon cancer, lung cancer, pancreatic cancer, ovarian cancer, cancer of the spleen, testicular cancer, cancer of the thymus, etc.,
A novel, specific, mammary cell growth inhibitor, Mammastatin, has recently been identified and characterized. Mammastatin has been expressed from variant clones, MammA (PCT/US97/18026, ATCC# 97451, deposited 22 Feb. 1996); MammB (PCT/US97/27147, ATCC# PTA-2091, deposited 15 Jun. 2000); and MammC, described in copending PCT application No. PCT/US00/16933, filed on even date herewith (ATCC# PTA-2090, deposited 15 Jun. 2000).
Mammastatin is produced and secreted by normal mammary cells, and is detected in blood samples of normal individuals. Blood concentrations of the mammary cell growth inhibitor, and particularly of the active, phosphorylated form of Mammastatin, are reduced or absent in breast cancer patients. Administration of protein comprising active Mammastatin (secreted from normal human breast cancer cells) is effective to reduce tumor size and number, and to prevent tumor growth in late stage cancer patients.
Epithelial cell growth inhibitors having similarity to Mammastatin have now been discovered, isolated, and characterized. These inhibitors bear partial sequence identity to Mammastatin at the 5′ end of the sequence, and have little or no identity at the 3′ end of the molecule. Like Mammastatin, the newly discovered family of epithelial cell growth inhibitors (ECGI) are differentially expressed in normal epithelial cell tissues, but not in cancerous epithelial cell tissues. Also, like Mammastatin, the newly discovered family of epithelial cell growth inhibitors are detected in blood samples taken from normal individuals, but not in the blood of patients with epithelial cell cancers, as shown in the Examples below.